Teràpia fotodinámica (PDT) i quimioterapia fotoactivada (PACT) en el tractament del cáncer: abast i limitacions

Tuneu Esquís, Guillem
Photodynamic therapy (PDT) is a clinically approved alternative treatment that bases its mechanism of action on a photosensitizer (PS) that is activated when irradiated with light, and that in the presence of molecular oxygen generates ROS that causes oxidative damage to cancer cells. The concept first emerged in 1900 when Raab observed that the combination of light and acridine had a lethal effect on a paramecium species. Later, in 1961 Lipson and Baldes confirmed that a derivative of porphyrin accumulated in the tumor tissue and emitted fluorescence. In 1993 a PS, the Photofrin, was approved for the first time to treat cancer. On the other hand, photoactivated chemotherapy (PACT) is an alternative treatment in development that does not yet have clinical applications. It relies its operation on a photocaged compound formed by a metallic part attached to another molecule that, when irradiated with light, breaks down and releases a specific therapeutic molecule for a target. The photocaged compounds were first used by Engels and Kaplan in the late seventies and since 2009 the term PACT has been used to refer to oncological strategies using these compounds. The main objective of this work has been, by means of a bibliographic search, to define the real scope and limitations of PDT and PACT, while posing its differential values and future prospects. PDT can be applied to treat different types of cancers, being especially effective in early superficial well oxygenated tumors. It can also be used as a diagnostic tool. However, it cannot currently be used in hypoxic tumors or in metastases, and the delivery of light in deep tumors can be complicated. The high selectivity for tumor tissue and the insignificant side effects it causes are its differential values. PDT can therefore be fully consolidated in the future, combined with other therapies, but also as a standalone treatment for oxygenated tumours. PACT’s mode of action gives it a differential value to treat multiple types of cancers, including hypoxic ones, without damaging healthy tissues. However, current PACT compounds do not absorb light efficiently enough and their photoactivation is irreversible. PACT's future prospects are promising if it improves its performance and finds a niche market where it can exploit its ability to treat tumors in a targeted manner ​
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